|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
In LSL-K-ras(G12D/+)Pten(loxP/loxP) mice with established intraperitoneal tumor disease, oral administration of NVP-BEZ235 decreased pAkt, p4E-BP1 and Ki67 in tumor tissue, and resulted in significantly longer survival compared to control animals (P < 0.05).
|
21372221 |
2011 |
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Treatment of Kras(G12D) mice with either of two distinct small molecule Pak inhibitors (PF3758309 and FRAX597) caused tumor regression and loss of Erk and Akt activity.
|
22983922 |
2012 |
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Furthermore, isoform-selective inhibitors showed a similar pattern of the isoform dependence in established Kras(G12D)/PTEN-deficient tumors.
|
24737887 |
2014 |
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Finally, m-CT imaging in live Kras(G12D-LSL) mice showed reduction of tumor burdens in PD-0325901-treated animals at sub-MTD dose.
|
22684718 |
2012 |
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Most genes from this signature are also upregulated in poorly differentiated tumors developing in Pten(thyr-/-),Kras(G12D) mice.
|
23509868 |
2013 |
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
We analyzed tumor growth in mice that expressed the oncogenic form of KRAS (KRAS(G12D)) in pancreatic precursor cells, as well as sst2+/- and sst2-/-, and in crossed KRAS(G12D);sst2+/- and KRAS(G12D);sst2-/- mice.
|
25683115 |
2015 |
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Moreover, we show that KRAS(G12D)- and BRAF(V600E)-induced tumor formation in an orthotopic model requires IGF1R.
|
22871572 |
2012 |
|
Carcinogenesis
|
|
0.020 |
GeneticVariation
|
BEFREE |
Tumorigenesis was measured in the Kras(G12D/+);Ptf1a(Cre/+) mouse model of PDA; these mice were crossed with mice with pancreas-specific disruption of genes encoding PI3K p110α (Pik3ca), p110β (Pik3cb), or RAC1 (Rac1).
|
25311989 |
2014 |
|
Malignant Neoplasms
|
|
0.020 |
GeneticVariation
|
BEFREE |
Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches.
|
25877892 |
2015 |
|
Neoplasm Metastasis
|
|
0.020 |
GeneticVariation
|
BEFREE |
In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases.
|
20541700 |
2010 |
|
Neoplasm Metastasis
|
|
0.020 |
GeneticVariation
|
BEFREE |
GTPase-impairing somatic mutations in RAS genes, such as KRAS(G12D), are among the most common oncogenic events in metastatic cancer.
|
26549032 |
2016 |
|
Primary malignant neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
Moreover, all mice with Kras(G12D) activation and Pten homozygous deletion succumbed to cancer by 3 weeks of age.
|
20807812 |
2010 |
|
Secondary Neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
GTPase-impairing somatic mutations in RAS genes, such as KRAS(G12D), are among the most common oncogenic events in metastatic cancer.
|
26549032 |
2016 |
|
Tumor Progression
|
|
0.020 |
GeneticVariation
|
BEFREE |
Additionally, we tested efficacy of PD-0325901 in Kras(G12D-LSL) conditional GEMMs (genetically engineered mouse models) which are a valuable tool in translational research to study tumor progression.
|
22684718 |
2012 |
|
Carcinogenesis
|
|
0.020 |
GeneticVariation
|
BEFREE |
Administration of a CXCL16-neutralizing antibody to KRAS(G12D) mice reduced activation of PI3K signaling to AKT and NF-κB, blocking carcinogenesis.
|
25683115 |
2015 |
|
Secondary Neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases.
|
20541700 |
2010 |
|
Primary malignant neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches.
|
25877892 |
2015 |
|
Malignant Neoplasms
|
|
0.020 |
GeneticVariation
|
BEFREE |
Moreover, all mice with Kras(G12D) activation and Pten homozygous deletion succumbed to cancer by 3 weeks of age.
|
20807812 |
2010 |
|
Tumor Progression
|
|
0.020 |
GeneticVariation
|
BEFREE |
We hypothesized that tumor progression was because of concomitant activation of the mitogen-activated protein kinase pathway downstream of Kras(G12D) expression promoting cell survival and that the therapeutic effect of PF-04691502 would be enhanced by combinatory inhibition of MEK using PD-0325901.
|
21632463 |
2011 |
|
ovarian neoplasm
|
|
0.010 |
GeneticVariation
|
BEFREE |
In vivo activity of combined PI3K/mTOR and MEK inhibition in a Kras(G12D);Pten deletion mouse model of ovarian cancer.
|
21632463 |
2011 |
|
Adenocarcinoma of lung (disorder)
|
|
0.010 |
GeneticVariation
|
BEFREE |
Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice.
|
22684718 |
2012 |
|
Hypocholesterolemia
|
|
0.010 |
GeneticVariation
|
BEFREE |
We show that chronic cholesterol depletion achieved with lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment results in a significant increase in apoptosis in HT-29 and Colo-205 cells containing the (V600E)B-RAF mutation, but not in HCT-116 and LoVo cells harbouring the (G13D)Ras mutation, or BE cells, which possess two mutations, (G13D)Ras and (G463V)B-RAF.
|
19700418 |
2009 |
|
Follicular thyroid carcinoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
We have generated mouse models that develop ATC ([Pten, p53](thyr-/-) mice) and follicular thyroid cancer with areas of poor differentiation (Pten(thyr-/-),Kras(G12D) mice).
|
23509868 |
2013 |
|
Pancreatic Neoplasm
|
|
0.010 |
GeneticVariation
|
BEFREE |
Pancreas-specific disruption of Pik3ca or Rac1, but not Pik3cb, prevented the development of pancreatic tumors in Kras(G12D/+);Ptf1a(Cre/+) mice.
|
25311989 |
2014 |
|
Malignant tumor of colon
|
|
0.010 |
GeneticVariation
|
BEFREE |
We examined the anti-proliferative effect of miR-143#12 and the mechanism in human colon cancer DLD-1 cell (G13D) and other cell types harboring K-Ras mutations.
|
29498789 |
2018 |